What is the recommended treatment for pyelonephritis?

Treatment of Pyelonephritis

For uncomplicated pyelonephritis, fluoroquinolones (ciprofloxacin or levofloxacin) are the first-line oral treatment options, while hospitalized patients should receive initial intravenous therapy with a fluoroquinolone, aminoglycoside (with or without ampicillin), or extended-spectrum cephalosporin. 1

Classification and Initial Assessment

Before initiating treatment, it's essential to distinguish between uncomplicated and complicated pyelonephritis:

• Uncomplicated pyelonephritis: Occurs in non-pregnant, premenopausal women with no urological abnormalities or comorbidities
• Complicated pyelonephritis: Occurs with host-related factors or anatomic/functional abnormalities that make infection harder to eradicate

Diagnostic Workup

• Urinalysis (white and red blood cells, nitrite)
• Urine culture with antimicrobial susceptibility testing (mandatory in all cases)
• Imaging considerations:
  • Ultrasound: For patients with history of urolithiasis, renal function disturbances, or high urine pH
  • CT scan or excretory urography: If patient remains febrile after 72 hours of treatment or clinical deterioration
  • For pregnant women: Ultrasound or MRI (to avoid radiation)

Treatment Algorithm for Uncomplicated Pyelonephritis

Outpatient Management (Mild to Moderate Cases)

Oral therapy options:

• Fluoroquinolones (first-line if local resistance <10%):
  • Ciprofloxacin 500-750 mg twice daily for 7 days
  • Levofloxacin 750 mg once daily for 5 days 1, 2
• Alternative oral options:
  • Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 14 days
  • Cefpodoxime 200 mg twice daily for 10 days
  • Ceftibuten 400 mg once daily for 10 days 1

Important note: If using trimethoprim-sulfamethoxazole or oral β-lactams when susceptibility is unknown, administer an initial intravenous dose of a long-acting parenteral antimicrobial (e.g., ceftriaxone 1g) 1

Inpatient Management (Severe Cases)

Initial IV antimicrobial options:

• Fluoroquinolones:
  • Ciprofloxacin 400 mg twice daily
  • Levofloxacin 750 mg once daily
• Cephalosporins:
  • Ceftriaxone 1-2 g once daily
  • Cefotaxime 2 g three times daily
  • Cefepime 1-2 g twice daily
• Aminoglycosides:
  • Gentamicin 5 mg/kg once daily
  • Amikacin 15 mg/kg once daily
• Extended-spectrum penicillins:
  • Piperacillin-tazobactam 2.5-4.5 g three times daily 1

Reserve for multidrug-resistant organisms:

• Carbapenems (imipenem/cilastatin, meropenem)
• Novel broad-spectrum agents (ceftolozane/tazobactam, ceftazidime/avibactam) 1

Treatment Duration and Transition to Oral Therapy

• Short outpatient course (5-7 days) is equivalent to longer therapy for clinical and microbiological success, though may have higher recurrence rates 1
• For hospitalized patients, consider early switch to oral therapy once clinical improvement occurs 3
• For β-lactam therapy, continue for 10-14 days 1

Special Considerations

Complicated UTI Factors

• Obstruction in urinary tract
• Foreign body presence
• Incomplete voiding
• Vesicoureteral reflux
• Recent instrumentation
• Male gender
• Pregnancy
• Diabetes mellitus
• Immunosuppression
• Healthcare-associated infections
• ESBL-producing or multidrug-resistant organisms 1

Antimicrobial Resistance Concerns

• Fluoroquinolone resistance is increasing (10-18% in some regions) 4
• Higher resistance rates in patients with recent quinolone treatment or hospitalization
• E. coli resistance to third-generation cephalosporins is rising rapidly (1% in 2005 to 10% in 2012) 4
• Local resistance patterns should guide empiric therapy choices

Common Pitfalls and Caveats

1. Failing to obtain urine culture: Always collect urine culture before starting antibiotics
2. Overlooking obstructive pyelonephritis: Prompt differentiation between uncomplicated and obstructive pyelonephritis is crucial, as the latter can rapidly progress to urosepsis
3. Inappropriate oral agents: Avoid nitrofurantoin, oral fosfomycin, and pivmecillinam for pyelonephritis due to insufficient efficacy data 1
4. Overuse of broad-spectrum antibiotics: Reserve carbapenems and novel agents for confirmed multidrug-resistant organisms
5. Inadequate follow-up: Consider imaging if fever persists beyond 72 hours of appropriate therapy
6. Ignoring local resistance patterns: Treatment should be tailored based on local antimicrobial resistance data

By following this evidence-based approach to pyelonephritis treatment, clinicians can optimize outcomes while practicing appropriate antimicrobial stewardship.